Steve Safe

Date: September 20, 2004

Dioxin to New Mechanism-Based Anticancer Drugs - Superfund Research

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related Superfund toxic chemicals activate the aryl hydrocarbon receptor (AhR) and induce toxic responses. Research in this laboratory has developed selective AhR modulators (SAhRMs), such as ring-substituted diindolylmethanes (DIMs), for chemotherapy of breast, endometrial, pancreatic and prostate cancer. Further modification of DIMs have resulted in a new series of anticarcinogenic AhR-inactive analogs. Studies on their mechanism of action has demonstrated that these methylene-substituted DIMs activate orphan nuclear receptors that induce genes associated with growth inhibition and cancer cell death.